In a study of 30 healthy women 65-75 years of age treated for 2 y with constant combined daily oral estrogen and low dose progestin compared with 30 age-matched female BLSA participants who do not receive ERT, 18 treated subjects completing one year showed significant decreases in depression, anger, and tension as measured by the Profile of Mood Scale (n=18), and significant decreases in vasomotor symptoms. In 16 completing the second year, there were significant increases in total body bone mineral density (3 plum minus 7%), and lumbar spine density (7 plum minus 1%) which correlated with decreases in biomarkers of bone resorption including urinary pyridinoline (30 plus minus 6%) and serum osteocalcin (35 plus minus 6%). There were also significant decreases in total cholesterol (6 plus minus 2%) and LDL cholesterol (14 plus minus 3%)and increases in HDL cholesterol (9 plus minus 4%). Adverse effects included breast swelling and tenderness and vaginal spotting which decreased from a mean of 2.3 plus minus 1.3 days/mo at 3 months to 0.3 [unreadable] .2 days/mo by 1 year. The positive effects on bone, lipids, and affect and minimal adverse effects, suggest that older women should be included in future randomized clinical trials of estrogen use in postmenopausal women. In a longitudinal study of changes in hormone regulation, bone and mineral metabolism, and glucose and lipid metabolism in healthy women during the menopausal transition, 87 women have completed a total of 297 GCRC outpatient visits ranging from 1 to11 visits per individual. Eight women have completed 12 GCRC inpatient visits for 12 hour nocturnal blood sampling. Cross-sectional data analyses comparing the endocrine profiles to the bone biochemistries, bone density measurements, and body composition assessments were begun in August 1995.